Morocco Reports Hypermorphism on pH1N1 HA and NA Fragments

Sequences discussed in this analysis are variously stored publicly at GenBank and at GISAID. We gratefully acknowledge the authors, originating and submitting laboratories of the sequences from GenBank and from GISAID’s EpiFlu™ Database on which this research is based. A GISAID-generated list is detailed in a linked spreadsheet for completeness in citation.

Last Update
2011-11-03

On 2011-10-25, the Institute Pasteur of Morocco deposited a group of human pH1N1 sequences at GenBank and GISAID.  HA segments include 14 fragments.  The NA segment is represented with 15 fragments, 7 that are related to a deposited HA fragment.  All sequences are marked geographically as Casablanca.  The sample dates span 2010-12-20 to 2011-04-01 with no specification of treatment protocol, clinical progression or clinical outcome.

Hypermorphic behaviour is found on 71% of the sequences that have both HA and NA segments, notwithstanding the fact that both segments are fragments across this deposit.  These 5 hypermorphic representatives are on two separate lineages. Additionally, the NA fragment of  MoroccoCasablanca69_11F_2011_01_26  [EPI340865] demonstrates significant, rare zoonotic homology to Avian H1N1, H5N1 and Avian H9N2.

Multi-clade hypermorphism in a single geography and within a contemporaneous time span merits careful evaluation.

Zoonoses of Polymorphisms

The mammal and avian database of Influenza A H13 covering all Neuraminidase forms comprises only 93 sequences, yet shares homology to pH1N1 human polymorphisms on Clade1.Upsilon as well as rare and novel pH1N1 human polymorphisms on Clade2, Clade4 and Clade5 sequences in this Moroccan deposit.  Several of these shared polymorphisms, e.g. markers for Clade5 (HA 219V and HA 252L), are previously uncharacterised as to potential Ultimate Origin.  The identification of multi-clade hypermorphism in this geography with wide homology to a single candidate animal reservoir (A/H13) solidifies the clear requirement for higher levels of avian surveillance.

Cladistics

10 - Clade2: 188T
01 - Clade4: 128D [EPI340861]
03 - Clade5: 208K_219V [EPI340881], [EPI340860], [EPI340876]

HA   84 Polymorphisms Averaging ~6.0 per Segment Fragment
NA 118 Polymorphisms Averaging ~7.9 per Segment Fragment

HA and NA 202 Total Polymorphisms Averaging ~13.9 per Sequence (Fragments)

Diversity

HA Superset – 36 Distinct Values
NA Superset - 47 Distinct Values

Two Receptor Binding Site items of interest are syn221P and 224K.  No indication is found of revisions at aa225, aa226 or aa230.  The Clade5 sequence bearing HA syn221P is contemporary in timing and homology to a small group of European Clade5 sequences.  A hypermorphic, Clade2 Moroccan sequence bears HA 224K, a polymorphism previously found in pH1N1 swine Clade5, suggesting a potential cross-clade transfer or compatibility.  The HA 224K may signal tissue tropism issues, having been documented on a lethal, neurotropic experimental strain (WSN_1933).

• [EPI340860] MoroccoCasablanca91_15mM_2011_02_02 – HA syn221P
• [EPI340866] MoroccoCasablanca69_11F_2011_01_26    – HA 224K

Hypermorphic Behaviour

04 HA Fragments >= 7 polymorphisms (29%)
13 NA Segments  >= 7 polymorphisms (87%)

Combined Polymorphic Count >= 15
5 of 7 Sequences with HA and NA Fragments (71%)
Total (HA / NA)

• 16 (HA 09 / NA 07): [EPI340881] MoroccoCasablanca117_10m_2011_02_15
• 16 (HA 07 / NA 09): [EPI340860] MoroccoCasablanca91_15mM_2011_02_02
• 16 (HA 05 / NA 11): [EPI340866] MoroccoCasablanca69_11F_2011_01_26
• 16 (HA 09 / NA 07): [EPI340876] MoroccoCasablanca23_3F_2011_01_13
• 15 (HA 09 / NA 07): [EPI340868] MoroccoCasablanca63_47F_2011_01_20

Sequences

. . . . MoroccoCasablanca124_5M_2011_04_01 (
. . . . . . . . GISAID NA EPI340879
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa36,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca211_15M_2010_12_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340885
. . . . . . . . 4 Polymorphisms (2 Amino and 2 Silent)
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa354)

. . . . MoroccoCasablanca117_10m_2011_02_15 (
. . . . . . . . Clade5: 208K_219V crossing with
. . . . . . . . . . . Clade2: 188T Defining Marker syn338G
. . . . . . . . GISAID HA EPI340881
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . syn47L (CTg) [H1N1 Avian],
. . . . . . . . syn82I (ATc) [H5N2 Avian],
. . . . . . . . syn93C (TGc) [H5N1 Avian Domestic & Wild],
. . . . . . . . . . . . . . . . . [H9N2 Avian Emergent 2009],
. . . . . . . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . 100N [H5N1 Egypt Avian 2009-2010
. . . . . . . . . . . . . . . with syn40H, syn55L, 192I, 196K],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008 with syn40H, syn55L],
. . . . . . . . . . . . [H5N2 Italy Avian 2005-2007],
. . . . . . . . . . . . [H7N3, H7N7, H9N2],
. . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 141Q (CAa) [H13 Avian (gAa, gga)],
. . . . . . . . syn170N (AAc) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 225G & 252L],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K (AaA) [pH1N1 Canine 2009],
. . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . [H3N2 Avian 2006, 2009],
. . . . . . . . 219V (gTA) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . [H13N2, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . syn338G (GGc) [Clade2, Rare to Clade5],
. . . . . . . . HA Truncated after aa342)

. . . . MoroccoCasablanca117_10m_2011_02_15 (
. . . . . . . . GISAID NA EPI340880
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . NA Truncated before aa33,
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn126P (CCt) [H1N1 Avian (Cat)],
. . . . . . . . . . . . . . . . . .[H9N2 Avian (Ctt)],
. . . . . . . . syn229S (TCc) [H1N1 Avian],
. . . . . . . . syn236G (GGc) [H1N1 Avian],
. . . . . . . . syn241V (GTg) [H1N1 Avian],
. . . . . . . . 299A,
. . . . . . . . 454V [Rare to pH1N1 (1)],
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca110_3F_2011_02_09 (
. . . . . . . . GISAID NA EPI340882
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa38,
. . . . . . . . 38V [H9N2 Avian],
. . . . . . . . syn60T (ACc) [H1N1 Avian Farm],
. . . . . . . . 81A [H1N1 Avian],
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 192N [H9N2 Avian (cac)],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca107_xF_2011_02_09 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340883
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#4,
. . . . . . . . 100N,
. . . . . . . . 173R,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa341)

. . . . MoroccoCasablanca103_5M_2011_02_07 (
. . . . . . . . GISAID HA EPI340884
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#7,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 324D [Novel to pH1N1],
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa350)

. . . . MoroccoCasablanca92_52F_2011_02_02 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340858
. . . . . . . . 8 Polymorphisms (6 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#3,
. . . . . . . . 22E [Novel to pH1N1],
. . . . . . . . 34T [Novel to pH1N1 2011],
. . . . . . . . 47Q [Novel to pH1N1],
. . . . . . . . 60V [H1N1 Avian],
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa341)

. . . . MoroccoCasablanca91_15mM_2011_02_02 (
. . . . . . . . Clade5: 208K_219V
. . . . . . . . GISAID HA EPI340860
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa82,
. . . . . . . . 100F [Novel to pH1N1],
. . . . . . . . syn102E (GAa) [H5N1 wt],
. . . . . . . . . . . . . . . . . [H9N2 Early Human wt, Human 2008],
. . . . . . . . . . . . . . . . . [H9N2 Avian wt],
. . . . . . . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . with 87N, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn170N (AAc) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 225G & 252L],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . 208K (AaA) [pH1N1 Canine 2009],
. . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . [H3N2 Avian 2006, 2009],
. . . . . . . . 219V (gTA) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . [H13N2, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . syn221P (CCt) [H3N2 Avian
. . . . . . . . . . . . . . . . . . . . . with 157S, 159S, syn287G],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human and Avian (tCt)],
. . . . . . . . . . . . . . . . . . [H5N1 Nigeria Avian (tCt)],
. . . . . . . . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . . with #1V, 87N, syn94Y, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with extensive Upsilon polymorphisms],
. . . . . . . . 252L (tTG) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . HA Truncated after aa352)

. . . . MoroccoCasablanca91_15mM_2011_02_02 (
. . . . . . . . GISAID NA EPI340859
. . . . . . . . 9 Polymorphisms (5 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa36,
. . . . . . . . 69V [H1N1 Avian],
. . . . . . . . 81A [H1N1 Avian],
. . . . . . . . 106M,
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn395G (GGg),
. . . . . . . . NA Truncated after aa452)

. . . . MoroccoCasablanca76_13M_2011_01_26 (
. . . . . . . . Clade4: 128D
. . . . . . . . GISAID HA EPI340861
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa13,
. . . . . . . . 28P [Novel to pH1N1.Clade4],
. . . . . . . . . . . [pH1N1 with Avian Influence (3)],
. . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . with 188T, syn210S, 225G & 252L],
. . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . with 188T, syn210S, 225G & 252L],
. . . . . . . . syn60I (ATc) [H9N2 Human and Avian Emergent],
. . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6,
. . . . . . . . . . . . . . . . . . . H13N8, H13N9 Avian (tTc)
. . . . . . . . . . . . . . . . . . . . . . with 28P, 188T, syn210S],
. . . . . . . . . . . . . . . . [1918],
. . . . . . . . 128D,
. . . . . . . . syn210S (AGt) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 28P, 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 28P, 188T, 225G & 252L],
. . . . . . . . 298V [H3N2 Avian, Canine, Feline & Mink],
. . . . . . . . . . . [H3N8],
. . . . . . . . . . . [H5 Avian, H6 Avian],
. . . . . . . . . . . [H9N2],
. . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . HA Truncated after aa341)

. . . . MoroccoCasablanca73_43F_2011_01_26 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340863
. . . . . . . . 6 Polymorphisms (4 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa0,
. . . . . . . . 11L [Novel to pH1N1],
. . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . with 28P, 188T, syn210S, 225G & 252L],
. . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . with 28P, 188T, syn210S, 225G & 252L],
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 259T [Recently Novel to pH1N1υ],
. . . . . . . . . . . . [H9N2 Avian and Human (att)
. . . . . . . . . . . . . . . . with syn40H],
. . . . . . . . . . . . [Not Found in H1N1 Swine with 124N],
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa338)

. . . . MoroccoCasablanca73_43F_2011_01_26 (
. . . . . . . . GISAID NA EPI340862
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . NA Truncated before aa44,
. . . . . . . . syn126P (CCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn293R (AGa) [H1N1 Avian Farm],
. . . . . . . . . . . . . . . . . . . [H5N1 Avian],
. . . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca69_11F_2011_01_26 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340866
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#5,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . 224K [swine pH1N1.Clade5]
. . . . . . . . . . . . [WSN_1933],
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa339)

. . . . MoroccoCasablanca69_11F_2011_01_26 (
. . . . . . . . GISAID NA EPI340865
. . . . . . . . 11 Polymorphisms (5 Amino and 6 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . 70N [H1N1 Avian],
. . . . . . . . syn137G (GGa) [H1N1 Avian],
. . . . . . . . syn215T (ACa) [H1N1 Avian],
. . . . . . . . 235D [H9N2 Avian],
. . . . . . . . syn240T (ACc) [H1N1 Avian],
. . . . . . . . 241I [H1N1 Avian],
. . . . . . . . 260R [H1N1 Avian],
. . . . . . . . 369K [H1N1 Avian],
. . . . . . . . syn377P (CCa) [H1N1 Avian],
. . . . . . . . syn386N (AAt) [H1N1 Environment],
. . . . . . . . syn416D (GAc) [H5N1 wt],
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca63_47F_2011_01_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340868
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa3,
. . . . . . . . syn90N (AAc) [Rare to pH1N1],
. . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa339)

. . . . MoroccoCasablanca63_47F_2011_01_20 (
. . . . . . . . GISAID NA EPI340867
. . . . . . . . 10 Polymorphisms (6 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa20,
. . . . . . . . syn89S (TCt) [H1N1 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 262N,
. . . . . . . . 263V [H1N1 Avian],
. . . . . . . . . . . . [H5N1 wt],
. . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 269I [H5N1 (tTa)],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 420C,
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca60_43F_2011_01_20 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340869
. . . . . . . . 5 Polymorphisms (2 Amino and 3 Silent)
. . . . . . . . HA Truncated before aa#3,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn205G (GGa),
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa338)

. . . . MoroccoCasablanca54_23F_2011_01_20 (
. . . . . . . . GISAID NA EPI340870
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa17,
. . . . . . . . 54L,
. . . . . . . . 81A [H1N1 Avian],
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn395G (GGg),
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca52_25F_2011_01_20 (
. . . . . . . . GISAID NA EPI340871
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa19,
. . . . . . . . 43R,
. . . . . . . . 44T,
. . . . . . . . 45L,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa452)

. . . . MoroccoCasablanca28_10M_2011_01_13 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340873
. . . . . . . . 5 Polymorphisms (3 Amino and 2 Silent)
. . . . . . . . HA Truncated before aa#6,
. . . . . . . . 100N,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . 340M,
. . . . . . . . HA Truncated after aa340)

. . . . MoroccoCasablanca28_10M_2011_01_13 (
. . . . . . . . GISAID NA EPI340872
. . . . . . . . 7 Polymorphisms (4 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa21,
. . . . . . . . 54V [H1N1 Avian],
. . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 454V [Rare to pH1N1 (1)],
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca26_24M_2011_01_13 (
. . . . . . . . Clade2: 188T
. . . . . . . . GISAID HA EPI340874
. . . . . . . . 6 Polymorphisms (3 Amino and 3 Silent)
. . . . . . . . 100N,
. . . . . . . . syn136T (ACt),
. . . . . . . . 176I,
. . . . . . . . syn179L (CTg),
. . . . . . . . 188T,
. . . . . . . . syn338G (GGc),
. . . . . . . . HA Truncated after aa353)

. . . . MoroccoCasablanca23_3F_2011_01_13 (
. . . . . . . . Clade5: 208K_219V
. . . . . . . . GISAID HA EPI340876
. . . . . . . . 9 Polymorphisms (4 Amino and 5 Silent)
. . . . . . . . HA Truncated before aa#7,
. . . . . . . . syn36L (tTA) [H5N1 Avian (tTg)],
. . . . . . . . syn47L (CTg) [H1N1 Avian],
. . . . . . . . 100N [H5N1 Egypt Avian 2009-2010
. . . . . . . . . . . . . . . . . with syn40H, syn55L, 192I, 196K],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008 with syn40H, syn55L],
. . . . . . . . . . . . [H5N2 Italy Avian 2005-2007],
. . . . . . . . . . . . [H7N3, H7N7, H9N2],
. . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . syn102E (GAa) [H5N1 wt],
. . . . . . . . . . . . . . . . . . . [H9N2 Early Human wt, Human 2008],
. . . . . . . . . . . . . . . . . . . [H9N2 Avian wt],
. . . . . . . . . . . . . . . . . . . [H10N7 Avian 2008
. . . . . . . . . . . . . . . . . . . . . . with 87N, 100N, syn102E,
. . . . . . . . . . . . . . . . . . . . . . . . 156E, 157E, 163T, 165N,
. . . . . . . . . . . . . . . . . . . . . . . . syn177L, 188T, syn221P, syn207S, syn213F,
. . . . . . . . . . . . . . . . . . . . . . . . 225G, 230I, 233H, 237I, syn239P,
. . . . . . . . . . . . . . . . . . . . . . . . syn338G, syn346G, syn356H,
. . . . . . . . . . . . . . . . . . . . . . . . syn390N, syn391T],
. . . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn170N (AAc) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . . . [H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . . . with 225G & 252L],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . . with extensive pH1N1υ polymorphisms],
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . . . . . . . . . . . [H13N2 Mammal],
. . . . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian],
. . . . . . . . . . . . . . . . . . [H1N1 Avian],
. . . . . . . . 208K (AaA) [pH1N1 Canine 2009],
. . . . . . . . . . . . . . . . [H1N1 Avian wt],
. . . . . . . . . . . . . . . . [H3N2 Avian 2006, 2009],
. . . . . . . . 219V (gTA) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . . . . . . . . . [H13N2, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 225G & 252L],
. . . . . . . . 252L (tTG) [H13N2 Mammal
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . . . . . . . . . [H13N2, H13N3, H13N6, H13N8, H13N9 Avian
. . . . . . . . . . . . . . . . . . . with 188T, 219V & 225G],
. . . . . . . . HA Truncated after aa335)

. . . . MoroccoCasablanca23_3F_2011_01_13 (
. . . . . . . . GISAID NA EPI340875
. . . . . . . . 7 Polymorphisms (3 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa39,
. . . . . . . . syn87G (GGg) [H9N2 Avian (aag)],
. . . . . . . . syn138A (GCt) [H1N1 Avian],
. . . . . . . . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 242V [H9N2 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . NA Truncated after aa455)

. . . . MoroccoCasablanca17_12F_2011_01_07 (
. . . . . . . . GISAID NA EPI340877
. . . . . . . . 8 Polymorphisms (3 Amino and 5 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . syn176S (TCg) [H1N1 Avian],
. . . . . . . . 213K,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn338V (GTg) [H1N1 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca15_35F_2011_01_06 (
. . . . . . . . GISAID NA EPI340878
. . . . . . . . 8 Polymorphisms (4 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa35,
. . . . . . . . syn126P (CCa),
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 263V [H1N1 Avian],
. . . . . . . . . . . . [H5N1 wt],
. . . . . . . . . . . . [H9N2 Avian],
. . . . . . . . 269I [H5N1 (tTa)],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa454)

. . . . MoroccoCasablanca07_23F_2011_01_05 (
. . . . . . . . GISAID NA EPI340864
. . . . . . . . 8 Polymorphisms (5 Amino and 3 Silent)
. . . . . . . . NA Truncated before aa34,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . 419S,
. . . . . . . . 420A,
. . . . . . . . 428I,
. . . . . . . . NA Truncated after aa453)

. . . . MoroccoCasablanca210_2010_12_20 (
. . . . . . . . GISAID NA EPI340886
. . . . . . . . 6 Polymorphisms (2 Amino and 4 Silent)
. . . . . . . . NA Truncated before aa17,
. . . . . . . . syn240T (ACc),
. . . . . . . . 241I,
. . . . . . . . syn273N (AAc) [H1N1 Avian],
. . . . . . . . 369K,
. . . . . . . . syn377P (CCa),
. . . . . . . . syn416D (GAc),
. . . . . . . . NA Truncated after aa457)

Supporting Sequences

. . . . NewYork7420_2010_01_02 (
. . . . . . . . GenBank HA CY065067
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . 35I [H5N1 Egypt Human 2009-2010],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . syn80S (TCt) [H5N1 Egypt Human 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . . . . . . . . . . . [H6N1, H7N3, H9N2, H11],
. . . . . . . . . . . . . . . . . . [H1N1 Avian
. . . . . . . . . . . . . . . . . . . . . with #1T, 8V, 22I, syn31H,
. . . . . . . . . . . . . . . . . . . . . . . . syn40H, syn42G, 72L,
. . . . . . . . . . . . . . . . . . . . . . . . syn81Y, syn82I, 87N
. . . . . . . . . . . . . . . . . . . . . . . . syn118E, 144E, 158E,
. . . . . . . . . . . . . . . . . . . . . . . . 189T, 200T, 218S, 218V,
. . . . . . . . . . . . . . . . . . . . . . . . 237I, syn287G, syn346G,
. . . . . . . . . . . . . . . . . . . . . . . . 453K, 502K, 523A, 523I],
. . . . . . . . syn159N (AAc) [H3N8 Avian & Equine],
. . . . . . . . . . . . . . . [H9N2],
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . 236I [H3N8],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008-2010],
. . . . . . . . . . . . [H6, H7N7, H9N2 2009, H11],
. . . . . . . . syn413K (AAg) [H1N1 Avian, H2, H5N1, H9N2],
. . . . . . . . syn441H (CAt) [H1N1 Avian, H2, H5N1, H6, H9N2, H11])

. . . . NewYork7425_2009_12_20 (
. . . . . . . . GenBank HA CY065091
. . . . . . . . 7 Polymorphisms (2 Amino and 5 Silent)
. . . . . . . . 35I [H5N1 Egypt Human 2009-2010],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . [H5N1 Egypt Avian 2007-2010],
. . . . . . . . syn113S (TCg) [1918],
. . . . . . . . syn159N (AAc) [H3N8 Avian & Equine],
. . . . . . . . . . . . . . . [H9N2],
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . 236I [H3N8],
. . . . . . . . . . . . [H5N1 Egypt Human Gharbiyah, 80% CFR],
. . . . . . . . . . . . [H5N1 Egypt Avian 2008-2010],
. . . . . . . . . . . . [H6, H7N7, H9N2 2009, H11],
. . . . . . . . syn413K (AAg) [H1N1 Avian, H2, H5N1, H9N2],
. . . . . . . . syn441H (CAt) [H1N1 Avian, H2, H5N1, H6, H9N2, H11])

. . . . Texas43242018_2009_07_24 (
. . . . . . . . GenBank HA CY051823
. . . . . . . . 5 Polymorphisms (0 Amino and 5 Silent)
. . . . . . . . syn184H (CAc) [Early pH1N1 Highly Zoonotic]
. . . . . . . . . . . . . . . . . . [swine pH1N1.Clade5],
. . . . . . . . . . . . . . . . . . [H2N3, H3N8],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Human Fatality 2010],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Equine 2009],
. . . . . . . . . . . . . . . . . . [H5N1 Egypt Avian 2009],
. . . . . . . . . . . . . . . . . . [H6, H7N3, H7N7, H9N2, H11],
. . . . . . . . syn239P (CCt) [H1N1 Avian],
. . . . . . . . syn297N (AAc) [H3N2 Asia Avian 1975-1977 with 159S, 453K],
. . . . . . . . . . . . . . . . . . [H3N8 Avian],
. . . . . . . . . . . . . . . . . . [H5N1],
. . . . . . . . . . . . . . . . . . [H9N2 Human, Avian, Equine and Seal wt],
. . . . . . . . . . . . . . . . . . [H9N2 Avian 2009],
. . . . . . . . syn453R (AGg) [H1N1 Avian],
. . . . . . . . syn525S (AGc) [H1N1 Avian])

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